The present invention relates to a novel Staphylococcus aureus antigen, and to a method for obtaining and using the antigen.
S. aureus causes several diseases in animals and in humans by various pathogenic mechanisms. The most frequent and serious of these diseases are bacteremia and its complications in hospitalized patients. In particular, S. aureus can cause wound infections and infections associated with catheters and prosthetic devices. Serious infections associated with S. aureus bacteremia include osteomyelitis, invasive endocarditis and septicemia. The problem is compounded by multiple antibiotic resistance in hospital strains, which severely limits the choice of therapy. In addition, S. aureus is a major cause of mastitis in dairy and beef cattle, where the infection causes a major loss of income.
A S. aureus vaccine would provide a solution for the problem of antibiotic resistance. At least eight different serotypes of S. aureus have been identified using polyclonal and monoclonal antibodies to capsular polysaccharide (CPS). Karakawa et al., J. Clin. Microbiol. 22:445 (1985). The contents of this document and all others listed herein are incorporated herein by reference.
Surveys have shown that approximately 85-90% of human clinical isolates, and a comparable, although somewhat lower percentage of animal clinical isolates, are capsular polysaccharide Type 5 or Type 8. An individual vaccinated with a vaccine containing Type 5 and Type 8 CPS antigens would be protected from infection by 85-90% of clinically-significant S. aureus strains, but a significant risk of infection still would exist. A vaccine containing antigens from the other six serotypes theoretically could provide 100% protection, but would require production and purification of six additional components. This would be untenable from a practical standpoint. On the other hand, an antigen common to the isolates not typeable as Type 5 or Type 8 would enable production of a vaccine containing only three antigens.
It is therefore an object of the present invention to provide a whole cell vaccine of cells that carry an antigen that is common to a large number of clinically-significant S. aureus strains, particularly one that is common to strains associated with infections in animals, particularly cattle.
It is a further object of the invention to provide a whole cell vaccine for prevention or treatment of infections in animals, particularly mastitis in cattle.
It is another object of the invention to provide a hyperimmune globulin composition that contains antibodies directed against bacteria that carry an antigen that is common to a large number of clinically-significant S. aureus strains, particularly one that is common to strains associated with infections in animals, particularly cattle.
It is yet another object of the invention to provide a hyperimmune globulin composition that is effective in treatment of infections in animals, particularly mastitis.
In accordance with these and other objects according to the invention, there is provided a whole cell vaccine comprising cells from a strain of Staphylococcus aureus that carries an antigen that comprises xcex2-linked hexosamine, that contains no O-acetyl groups detectable by nuclear magnetic resonance spectroscopy and that reacts with antibodies to ATCC 55804. Also provided is a composition comprising the whole cell vaccine, and a sterile, pharmaceutically-acceptable carrier therefor. The vaccine can be administered to a human or animal subject to provide protection against S. aureus infection. It is particularly useful in preventing mastitis in animals.
An immunotherapeutic agent against S. aureus infection, particularly against mastitis in animals, can be prepared by immunizing human or animal subjects with a composition according to the invention, collecting plasma from the immunized subjects, and harvesting a human or veterinary hyperimmune globulin that contains antibodies directed against S. aureus from the collected plasma. The hyperimmune globulin contains antibodies directed against the xcex2-linked hexosamine antigen. An immunotherapy method comprises a step of administering this hyperimmune globulin to a human or animal subject, especially an animal with mastitis, to prevent or treat infection.
Other objects, features and advantages of the present invention will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.